Methods
A total of 969 patients hospitalized between April 2020 and January 2021
were screened in this retrospective study. Two hundred ninety-three
participants with polymerase chain reaction confirmed COVID-19 were
divided into the favipiravir group (n=159) and the HQ group (n=135).
Patients not meeting the criteria were excluded from the study
(Table-1). Finally, 101 participants in the favipiravir group and 93 in
the HQ group were included in the study (Figure-1).
Healthcare system algorithms have been applied to the treatment of
patients. HQ, azithromycin, and oseltamivir triple therapy were given to
patients hospitalized until July 2, 2020. Afterward, algorithms switched
to favipiravir and levofloxacin. The authors compared the arrhythmic
adverse effects between the two groups. HQ group treatment regimen were;
HQ 200 mg orally twice a day for five days, azithromycin 500 mg orally
once daily for five days, and subcutaneous enoxaparin 1 mg/kg.
Favipiravir group protocol was as follows; favipiravir 1600mg loading
dose, 600mg twice daily for four days, levofloxacin 500 once a day for
five days, and subcutaneous enoxaparin 1 mg/kg. Symptom-based
medications such as ceftriaxone, paracetamol, pantoprazole,
dexamethasone were given in both groups.
Demographics, clinical characteristics, laboratory data, medications,
outcomes, basal and predischarge electrocardiography (ECG) were obtained
from the patient data registry. Electrolyte levels that could trigger
arrhythmia, troponin, D-dimer, and C-reactive protein were examined in
all participants. Inpatient medications and hemodynamic parameters such
as heart rate, blood pressure, and oxygen saturation were reconsidered
daily. The present study was approved by the local ethics committee and
the Ministry of Health Scientific Research Platform
(2021-02-15T01_58_28). Written and signed informed consent was
obtained from the participants.
A standard 12-lead ECG (Cardiofax m, NIHON KOHDEN Corp. Tokyo, Japan)
was performed at admission and discharge. Baseline and final ECGs of the
participants were compared. The following data were analyzed in the
admission and predischarge ECG or ECG during the arrhythmia; rhythm,
heart rate (HR), QRS duration, PR and QT interval, extrasystole, and
conduction disturbance. All parameters were manually measured from an
ECG by the same cardiologist. The physician employed Lead-II to analyze
rhythm, QRS duration, PR, and QT interval on ECG. If lead-II was not
applicable, lead-I was assessed. Bazett formula was utilized to
calculate the corrected QT (QTc) interval. The QTc prolongation was
defined as > 440 ms in males, >460 ms in
females.
The primary analysis was an evaluation of the arrhythmogenic adverse
effects of the favipiravir and HQ groups. The Shapiro-Wilk test
evaluated the normal distribution of variables. Continuous and
categorical variables were given as mean±SD or median (IQR) and
percentage, respectively. According to the data’s distribution, the
groups’ variables were compared using the student t-test or Mann-Whitney
U test and the chi-square test or Fisher’s exact test. Paired samples
t-test was applied to evaluate for initial and final ECG measurements
within groups. Statistical analyses were undertaken using the SPSS
version 22.0 software package (IBM SPSS, New York, USA) and MedCalc
version 15.8 statistical software (Ostend Belgium). The statistical
significance threshold was adjusted as p <0.05.